Accuracy of Peripheral Quantitative Computed Tomography (pQCT) For Assessing Area and Density of Mouse Cortical Bone

Abstract

Peripheral quantitative computed tomography (pQCT) is increasingly used for measurement of cortical bone geometry and density in mice. We evaluated the accuracy of pQCT for area and density measurements of thin-walled aluminum phantoms and mouse femora. Aluminum tubes with varying wall thicknesses and femora from 1- to 6-month-old C3H/HeJ (C3H) and C57B1/6J (B6) mice (average cortical thickness 0.14-0.29 mm) were scanned at 70- or 90-microm resolution. pQCT values of area were compared to optical values determined after sectioning, while pQCT density (vBMD) was compared to solid aluminum density or correlated to bone ash content. For the aluminum phantoms, the error in pQCT area and density depended strongly on wall thickness, and density was consistently underestimated. For mouse femora, threshold values were found that produced zero error in bone area for each strain and age group, although the optimal threshold differed between groups. pQCT vBMD correlated strongly with ash content (r2=0.7), although the regression equations differed between strains and the magnitude of the inter-strain difference in vBMD was fourfold greater than the difference in ash content. This finding suggests that pQCT can overestimate the differences in volumetric mineral density between inbred mouse strains whose bones are of different thickness (e.g., C3H vs. B6). In conclusion, both area and density values obtained by pQCT depend strongly on specimen thickness, consistent with a partial volume averaging artifact. Investigators using pQCT to assess cortical bones in mice should be aware of the potential for cortical thickness-dependent errors.

Dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and micro-computed tomography techniques are discordant for bone density and geometry measurements in the guinea pig

“…An object thickness-to-voxel size ratio of 9:1 or less had been associated at least 15 % error in density measurements in mouse femoral cortical bone [27]. This was consistent with the Bland-Altman plots, where deviation in metaphyseal vBMD among methods was inversely related to the magnitude of the measurements.…”

A physical phantom for the calibration of three‐dimensional X‐ray microtomography examination

“…Consequently, the thicknesses of the contained structures have to be in this range. An easy-to-handle material with an attenuation coefficient ( µ ) similar to bone and already used for calibration scopes in radiology is aluminium ( µ Al(30 keV) = 3.04 cm − 1 , µ cortical bone(30 keV) = 2.56 cm − 1 ) (Kalebo & Strid, 1988;Hubbel & Seltzer, 1995;Brodt et al ., 2003).…”

Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD

“…[2, 3] To overcome the challenges of DXA, peripheral quantitative computed tomography (pQCT) has been used to separate trabecular bone from cortical bone and estimate mechanical strength. [4, 5] While pQCT can assess both mineral content and structural properties in three dimensions from the same scan, its relatively low resolution can lead to errors when scanning small specimens [6, 7]. The resolution of micro-computed tomography (μCT) images is superior to clinical pQCT and, as a result, μCT has become the standard for accurate morphological and mineral density measurements in many pre-clinical studies [7].…”